Dr. Shakhnovich Receives NIH Grant to study Effect of Obesity on Pantoprazole Pharmacokinetics and Pharmacodynamics in Children

Valentina Shakhnovich, MD, Gastroenterology/Clinical Pharmacology, received a five-year $944,579 Mentored Patient-Oriented Research Career Development Award (K23) from the National Institutes of Health.

Dr. Shakhnovich’s study “Effect of Obesity on Pantoprazole Pharmacokinetics and Pharmacodynamics in Children” builds on her recently published findings, from two independent prospective investigations, that demonstrate reduced drug clearance and increased systemic exposure to the proton pump inhibitor (PPI) pantoprazole for obese children.

This finding means that children with obesity don’t always need higher doses of medications, at least not PPIs. Using intravenous pantoprazole as a model drug probe for the drug metabolizing pathway CYP2C19, Dr. Shakhnovich is now testing the hypothesis that increased fat in the liver underlies the observed reduction in PPI clearance and examining the impact this reduced clearance has on drug effect. This research represents the first step in developing individualized drug dosing recommendations currently lacking for children with obesity (1 in 5 children in the U.S.).

“Understanding of the biologic and physiologic mechanisms underlying altered drug metabolism and clearance is the first step toward developing accurate predictive models for optimizing the dose selection of PPIs, and other drugs commonly prescribed to children with obesity and related comorbidities,” she wrote.

As an outcome of the work proposed, Dr. Shakhnovich expects to generate a physiologically-based pharmacokinetic and pharmacodynamic computer tool to bridge the critical information gap regarding optimal dose selection of medications for obese children.